Safety and Efficacy of Endovascular Aortic Repair for Abdominal Aortic Aneurysms with a Hostile Neck Anatomy

Objective This study aimed to investigate the safety and efficacy of endovascular aortic repair(EVAR)for the treatment of an abdominal aortic aneurysm(AAA)with a hostile neck anatomy(HNA).Methods From January 1,2015 to December 31,2019,a total of 259 patients diagnosed with an AAA who underwent EVAR were recruited into this study.Based on the morphological characteristics of the proximal neck anatomy,the patients were divided into the HNA group and the friendly neck anatomy(FNA)group.The patients were followed up for up to 4 years.Results The average follow-up time was 1056.1±535.5 days.Type I endoleak occurred in 4 patients in the HNA group,and 2 patients in the FNA group.Neither death nor intraoperative switch to open repair occurred in either group.The time of the operation was significantly longer in the HNA group(FNA vs.HNA,99.2±51.1 min vs.117.5±63.8 min,P=0.011).There were no significant differences in short-term clinical success rate(P=0.228)or midterm clinical success rate(P=0.889)between the two groups.The overall mortality rate was 10.4%,and Kaplan-Meier survival analysis indicated that the two groups had similar cumulative survival rates at the end of the follow-up period(P=0.889).Conclusion EVAR was feasible and safe in patients with an AAA with a proximal HNA.The early and midterm results were promising;however,further studies are needed to verify the long-term effectiveness of EVAR.

Kunming mouse strain is less susceptible to elastase-induced abdominal aortic aneurysms

Background:Porcine pancreatic elastase(PPE)is successfully used to induce abdominal aortic aneurysm(AAA)in mice.However,differences between mouse strains in susceptibility to PPE induction have been reported.Kunming mouse is one of the most frequently used strains in China but whether it is suitable for induction of AAA by PPE application remains unclear.Methods:PPE infusion(1.5 units/ml)in temporary controlled aorta was performed to induce AAAs in both C57BL/6J and Kunming mice.Phosphatebuffered saline(PBS)application was used as vehicle control.The aorta diameters of all mice were measured at days 0 and 14 after surgery to evaluate the AAA formation.Results:After 14 days of PPE or PBS infusion,all mice were sacrificed and aorta tissues were collected for histological staining analysis.At the 14th day after infusion,PPE successfully induced aortic dilation in Kunming mice and typical AAA in C57BL/6J mice.The aorta diameter increased by 0.23 mm in Kunming mice after PPE infusion,while it was 0.72 mm in the C57BL/6J strain.PPE induced mild elastin degradation,smooth muscle cell(SMC)depletion and mural leucocyte infiltration in Kunming mice,but in PPE-sensitive C57BL/6J mice,it induced total loss of SMCs,elastin disappearance and diffused infiltrated leucocytes in aortic aneurysmal segments.The effects of PPE in inducing angiogenesis and upregulating matrix metalloproteinase 2 and 9 expression in Kunming mice were also weaker than that in C57BL/6J mice.Conclusion:At the reported dose of PPE,Kunming mouse is not as susceptible to AAA formation as C57BL/6J mice.The failure of PPE to induce AAA formation in Kunming mice may be associated to its inability to boost a strong inflammatory response.

Progression and Regression of Abdominal Aortic Aneurysms in Mice

Objective:Abdominal aortic aneurysm(AAA)is a significant medical problem with a high mortality rate.Nevertheless,the underlying mechanism for the progression and regression of AAA is unknown.Methods:Experimental model of AAA was first created by porcine pancreatic elastase incubation around the infrarenal aorta of C57BL/6 mice.Then,AAA progression and regression were evaluated based on the diameter and volume of AAA.The aortas were harvested for hematoxylin-eosin staining(HE),orcein staining,sirius red staining,immunofluorescence analysis and peris’prussian blue staining at the indicated time point.Finally,P-aminopropionitrile monofumarate(BAPN)was used to explore the underlying mechanism of the regression of AAA.Results:When we extended the observation period to 100 days,we not only observed an increase in the AAA diameter and volume in the early stage,but also a decrease in the late stage.Consistent with AAA diameter and volume,the aortic thickness showed the same tendency based on HE staining.The elastin and collagen content first degraded and then regenerated,which corresponds to the early deterioration and late regression of AAA.Then,endogenous up-regulation of lysyl oxidase(LOX)was detected,accompanying the regression of AAA,as detected by an immunofluorescent assay.BAPN and LOX inhibitor considerably inhibited the regression of AAA,paralleling the degradation of elastin lamella and collagen.Conclusion:Taken together,we tentatively conclude that endogenous re-generation of LOX played an influential role in the regression of AAA.Therefore,regulatory factors on the generation of LOX exhibit promising therapeutic potential against AAA.

Value of digital subtraction angiography in endovascular graft exclusion for abdominal aortic aneurysms

Objective: To evaluate the value of digital subtraction angiography (DSA) in management of endovascular graft exclusion (EVGE) for abdominal aortic aneurysms. Methods: Monitored by DSA and fluoroscopy, stent-graft complex were introduced into the aneurysm sac via femoral arteries and were deployed at the proximal and distal necks to exclude the sac from circulation. Results: The success rate of deployment was 94. 74% (36/38). Endoleaks occurred in 4 cases. One converted to open surgery because of sac rupture 4 days after deployment. Thrombosis and stenosis occurred in 2 cases. Three patients died shortly after the operation (< 3 months). Conclusion: DSA can monitor EVCE on real-time throughout the whole procedure. It can meet the needs of measurement, location, evaluating, detecting, and also can be much helpful in correcting complications. Moreover, it provides large visual field and operating space, and is a very important monitoring method for EVGE.

Standards of endovascular graft exclusion for abdominal aortic aneurysms

Objective: To discuss the standards of endovascular graft exclusion (EVGE) for abdominal aortic aneurysms (AAAs). Methods: The results of our primary experiences for the evidence of standards was summarized. Results: Standards of operating success, cure and procedure failure were put forward. Some relative questions on EVGE were also answered. Conclusion: EVGE is a kind of new conceptive therapy for AAAs in China. More cases should be evaluated in the future to modify it.

Endovascular stent graft repair of abdominal aortic aneurysms:Current status and future directions

Endovascular stent graft repair of abdominal aortic aneurysm(AAA)has undergone rapid developments since it was introduced in the early 1990s.Two main types of aortic stent grafts have been developed and are currently being used in clinical practice to deal with patients with complicated or unsuitable aneurysm necks,namely,suprarenal and fenestrated stent grafts.Helical computed tomography angiography has been widely recognized as the method of choice for both pre-operative planning and post-operative followup of endovascular repair(EVAR).In addition to 2D axial images,a number of 2D and 3D reconstructions are generated to provide additional information about imaging of the stent grafts in relation to the aortic aneurysm diameter and extent,encroachment of stent wires to the renal artery ostium and position of the fenestrated vessel stents.The purpose of this article is to provide an overview of applications of EVAR of AAA and diagnostic applications of 2D and 3D image visualizations in the assessment of treatment outcomes of EVAR.Interference of stent wires with renal blood flow from the hemodynamic point of view will also be discussed,and future directions explored.

Influence of periodontitis on abdominal aortic aneurysms

Periodontitis is known to be a risk factor for abdominal aortic aneurysm(AAA). However, the influence of periodontitis on AAA development is to be elucidated. This article is to review the relationship between periodontitis and AAA. We focused on the roles of specific periodontopathic bacteria in AAA, matrix metalloproteinases and toll-like receptors in the pathophysiology in the section of experimental analysis. Furthermore, we showed clinical data of periodontitis in patients with AAA. We concluded that periodontal pathogens play a critical role in the AAA development.

Surgical repair of thoracoabdominal aortic aneurysms using the critical artery reattachment technique

In the study, we sought to retrospectively analyze the effectiveness and safety of surgical repair of thoracoab-dominal aortic aneurysm using the critical artery reattachment technique. Twenty-three consecutive thoracoab-dominal aortic aneurysm patients were treated using the technique of sequential aortic clamping and critical artery reattachment. The entire procedure was technically successful in all patients. One died of renal failure and the overall hospital mortality was 4.35%. The total incidence of complications was 21.74%. At a median follow-up of 33 months, all patients were alive. We found that the application of critical artery reattachment technique in the management of thoracoabdominal aortic aneurysm provides excellent short- and mid-term results in most patients. It could markedly increase the curing rate and reduce the morbidity of postoperative complications including par-aplegia, ischemia of abdominal viscera, and renal failure.

Elevated plasma level of matrix metalloproteinases-9 and its significance in patients with abdominal aortic aneurysms

Objective: To investigate the changes of the plasma level of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the patients with abdominal aortic aneurysms (AAAs) before and after the treatment, and evaluate the significance of MMP-9 in the pathogenesis of AAAs. Methods: Blood samples of 35 patients with AAAs and 10 patients with the arterial occlusive diseases (AODs) , which enrolled into the Vascular Surgery Center of Colonge University Hospital from February to August of 2002, were collected before and one month after surgical repair or less-invasive endovascular exclusion. The plasma concentrations of MMP-9 of all the collected samples were measured by means of enzyme-linked immunosorbent assay(ELISA), and compared between the two groups patients at different time point. Results: The mean plasma concentration of MMP-9 of AAAs was significantly higher than that of AODs prior to treatment [(90.3±9.1) ng/ml vs (23.6±7.3) ng/ml, P<0.05], and no apparent difference was showed in the patients with AODs [(23.6±7.3) ng/ml vs (25.3±5.8) ng/ml, P>0.05)] before and after the surgical bypass operation. However, in the patients with AAAs the plasma concentration of MMP-9 was apparently decreased one month after the surgical repair or endovascular exclusion compared with before [(28.6±8.4) ng/ml vs (90.3±9.1) ng/ml, P<0.05)]. No meaningful difference of the mean plasma MMP-9 concentration was seen between two groups after the both being successfully treated [(28.6±8.4) ng/ml vs (25.3±5.8) ng/ml, P>0.05]. Conclusion: Apparent elevation of plasma concentration of MMP-9 in the AAAs and its dramatic decrease after being treated implicated that MMP-9 might play an important role in the formation and development of AAAs. Meanwhile, to investigate the changes of MMP-9 level of AAAs could provide an practical way to facilitate the earlier diagnosis and long term surveillance for AAAs. More importantly, pharmacologic prevention and treatment of AAAs, in which the MMP-9 serves as effective target, might be possible in the future.

Nitric oxide production and inducible nitric oxide synthase protein expression in human abdominal aortic aneurysms and cultured aneurismal smooth muscle cells

Objective:To investigate the production of nitric oxide(NO) and the expression of indurible nitric oxide synthase (iNOS). and their possible role in abdominal aortic aneurysm (AAA). Methods: A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszel X2 test and Kendall correlation. Results: Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P<0. 05) and the patients with occlusive arteries (P<0. 05). iNOS protein and media NOx (nitrite + nitrate) also increased in cultured SMCs from human AAA (n = 4, P<0. 05), while plasma NOx decreased in patients with AAA (n = 25) compared to the healthy controls (n = 20). There was a positive correlation between iNOS protein and the degree of inflammation in aneurismal wall (Kendall coefficient = 0. 5032, P = 0. 0029). Conclusion: SMCs and inflammatory cells are main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation, SMCs and oxidative stress.

Experimental and computational studies on the flow fields in aortic aneurysms associated with deployment of AAA stent-grafts

Pulsatile flow fields in rigid abdominal aortic aneurysm （AAA） models were investigated numerically, and the simulation results are found in good agreement with particle image velocimetry （PIV） measurements. There are one or more vortexes in the AAA bulge, and a fairly high wall shear stress exists at the distal end, and thus the AAA is in danger of rupture. Medical treatment consists of inserting a vascular stent-graft in the AAA, which would decrease the blood impact to the inner walls and reduce wall shear stress so that the rupture could be prevented. A new computational model, based on porous medium model, was developed and results are documented. Therapeutic effect of the stent-graft was verified numerically with the new model.

The incidence rate and histological characteristics of intimal hyperplasia in elastase-induced experimental abdominal aortic aneurysms in mice

Intimal hyperplasia(IH)is a negative vascular remodeling after arterial injury.IH occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse models.This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.A retrospective study was conducted by including 42 male elastaseinduced mouse AAA models.The IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were analyzed.Among 42 elastase-induced AAA mouse models,10 mice developed mild IH(24%)and severe IH was found in only 2 mice(5%).The outer diameters of the AAA segments in mice with and without IH did not show significant difference.Both mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH lesions.There was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe IH.However,only a lower numbers of T cells and B cells were found in the IH lesion.Local cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe lesions.In conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA model.This will help researchers better understand this model,and optimize it for use in AAA-related research.

Mesenchymal stem cells for treatment of aortic aneurysms

An aortic aneurysm(AA) is a silent but life-threatening disease that involves rupture. It occurs mainly in aging and severe atherosclerotic damage of the aortic wall. Even though surgical intervention is effective to prevent rupture, surgery for the thoracic and thoraco-abdom-inal aorta is an invasive procedure with high mortality and morbidity. Therefore, an alternative strategy for treatment of AA is required. Recently, the molecular pathology of AA has been clarified. AA is caused by an imbalance between the synthesis and degradation of extracellular matrices in the aortic wall. Chronic inflam-mation enhances the degradation of matrices directly and indirectly, making control of the chronic inflamma-tion crucial for aneurysmal development. Meanwhile, mesenchymal stem cells(MSCs) are known to be ob-tained from an adult population and to differentiate into various types of cells. In addition, MSCs have not only the potential anti-inflammatory and immunosuppres-sive properties but also can be recruited into damagedtissue. MSCs have been widely used as a source for celltherapy to treat various diseases involving graft-versus-host disease, stroke, myocardial infarction, and chronicinflammatory disease such as Crohn's disease clinically.Therefore, administration of MSCs might be availableto treat AA using anti-inflammatory and immnosup-pressive properties. This review provides a summary ofseveral studies on "Cell Therapy for Aortic Aneurysm"including our recent data, and we also discuss the pos-sibility of this kind of treatment.

The Elevated Expression of Osteopontin and NF-κB in Human Aortic Aneurysms and Its Implication

The expression and significance of osteopontin （OPN） and NF-κB in patients with thoracic aortic aneurysm （TAA） and abdominal aortic aneurysm （AAA） were investigated. Thirteen TAA specimens, 20 AAA specimens and 6 normal aortic specimens were collected. The expression of OPN, nuclear factor-κB P65 （NF-κB P65）, urokinase plasminogen activator （uPA）, matrix metalloproteinase-2 （MMP-2） and matrix metalloproteinase-9 （MMP-9） were detected by using immunohisto-chemistry and Western blotting was employed to determine the expression of OPN and NF-κB P65. Immunohistochemical results showed that the expression of OPN, NF-κB P65, uPA, MMP-2 and MMP-9 was positive in all TAA and AAA specimens and negative in normal specimens, with the difference being statistically significant （P〈0.05）. There was no difference in the expression between TAA and AAA specimens （P〉0.05）. Correlation analysis revealed that there existed a positive correlation between the expression of OPN and that of NF-κB P65, uPA, MMP-2 and MMP-9 and between the expression of NF-κB P65 and that of uPA, MMP-2, MMP-9 （P〈0.05）. Western blotting demonstrated that OPN and NF-κB P65 were positive in AAA and TAA specimens, and negative in normal specimens with the differences being statistically significant （P〈0.05）. There were no statistically significant differences in the expression of OPN and NF-κB P65 between AAA and TAA specimens （P〉0.05）. It was concluded that OPN and NF-κB P65 were involved in the pathogenesis of TAA and AAA. OPN can up-regulate the expression of MMP and uPA via NF-κB signaling pathway thereby accelerating the degradation of extracellular matrix and playing an important role in the pathogenesis and development of TAA and AAA.

Long-Term Results (Seven and More Years) of Sparing Treatment of Subjects with Descending Aortic Aneurysms

Descending aortic aneurysms (DAAs), including dissecting aneurysms (DA) have a multifactorial etiology and pathogenesis, therefore raising questions about the leading role of operative treatment to repair the lesion. Objective: To investigate remote (7 and more years) results of treatment in patients with DAAs in operative treatment only if there is a danger of aneurysm rupture. A total of 82 patients with atherosclerotic DAA identified between 2008 and 2011, and 22 patients with type 1 or 3 DeBakey dissecting aneurysms (DA) who had not been operated in the acute period due to a number of reasons were examined. The follow-up period of these groups was 7 or more years. When using a sparing treatment to treat DAA, we saw survival of 90.1 at 2 years, 76.8% at 4 years, 59.4% at 6 years, and 57.5% at 7 years with the uniform increase in mortality rate, mainly due to a comorbidity. Survival in DA group (77.3%) was better due to a younger age and was 68.4% in operated and 54% in non-operated patients at 7 years. It is symptomatic that the aneurysm rupture rate was not always affected by operative treatment. Therefore, it seems like medical treatment is more consistent with etiopathogenesis of the disease compared to surgery during the stabilization period.

Atherosclerotic Descending Aortic Aneurysms. Pros and Cons of Surgery

Within the last few years, there has been a strong trend to rethink the issue of management of atherosclerotic descending thoracic and abdominal aortic aneurysms (AAAs). When etiopathogenetic associations among changes observed during the progression of the disease were not fully described, surgeons had successfully applied, although traumatic, but a rather radical method to rescue from the rupture threat. As we gained experience and knowledge about long-term outcomes, mostly concerned mortality, we realized that surgery could not be the main tactical approach to AAAs treatment due to its frequent inefficiency and failure to guarantee that the disease would be suppressed including co-morbidities, polymorphic processes and clinical manifestations. It all required more sparing treatment strategies. The situation gave rise to a more argumentative and sparing medical-and-surgical approach to treatment based on a more in-depth understanding of the etiopathogenesis of the disease whereas surgery would remain of prime importance when appropriate. The following has been developed to improve treatment outcomes for AAA: 1) Multifactorial determination of indications for surgical correction with outlining the area of relative and absolute risk of aneurysm rupture;2) Method of conservative treatment aimed to attain and maintain optimal blood pressure, target levels of cholesterol and low-density lipoproteins, as well as reduce oxidative and inflammatory processes in aorta, strengthen its wall, stabilize the disease and control co-morbidities. A four-year follow-up of patients using this developed technology has yielded more preferred results suggesting the need for narrowing indications for surgery to treat AAAs. Another advantage of the sparing approach to treat AAA is economic, due to fewer operations and implantations of stent-grafts, considering the fact that medical treatment should be used in operated subjects, too.

Long-term outcomes following exclusive use of endovascular aortic repair for ruptured infrarenal abdominal aortic aneurysms

To the Editor:Ruptured abdominal aortic aneurysm(rAAA)is a fatal disease.Emergency surgery is the only way to provide an opportunity for survival.In 1994,endovascular aortic repair(EVAR)was reported as an emergency treatment for rAAA.Compared with traditional open surgery(OS),patients could benefit from its lower perioperative mortality and minimal invasiveness.Although recent guidelines have recommended an EVARfirst approach if suitable as judged by the clinician,the standard of whether to give a priority to EVAR varies among clinicians in practical applications,because hostile aortic morphology and hemodynamic conditions were thought to weaken the benefit of EVAR.Hence,controversies still exist regarding whether EVAR as a priority is applicable to most rAAAs.In addition,a search of the literature found few population-based studies with long-term outcomes.Given this,a population-based study was conducted by Zhongshan Hospital,Fudan University.

Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms

Abdominal aortic aneurysm(AAA)is a progressive aortic dilatation,causing~80%mortality upon rupture.Currently,there is no approved drug therapy for AAA.Surgical repairs are invasive and risky and thus not recommended to patients with small AAAs which,however,account for~90%of the newly diagnosed cases.It is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA progression.We contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery methods.There is substantial evidence that degenerative smooth muscle cells(SMCs)orchestrate AAA pathogenesis and progression.In this study,we made an exciting finding that PERK,the endoplasmic reticulum(ER)stress Protein Kinase R-like ER Kinase,is a potent driver of SMC degeneration and hence a potential therapeutic target.Indeed,local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in vivo.In parallel,we also conceived a biomimetic nanocluster(NC)design uniquely tailored to AAA-targeting drug delivery.This NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating;and when loaded with a selective PERK inhibitor(PERKi,GSK2656157),the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of AAA.In summary,our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis,but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.

Complex pathologies of angiotensin Ⅱ-induced abdominal aortic aneurysms

Angiotensin Ⅱ (AngⅡ) is the primary bioactive peptide of the renin angiotensin system that plays a critical role in many cardiovascular diseases.Sub-cutaneous infusion of AngⅡ into mice induces the development of abdominal aortic aneurysms (AAAs).Like human AAAs,AngⅡ-induced AAA tissues exhibit progressive changes and considerable heterogeneity.This complex pathology provides an impediment to the quantification of aneurysmal tissue composition by biochemical and immunostaining techniques.Therefore,while the mouse model of AngⅡ-induced AAAs provides a salutary approach to studying the mechanisms of the evolution of AAAs in humans,meaningful interpretation of mechanisms requires consideration of the heterogeneous nature of the diseased tissue.

Clinical experience with multiple stents in complex thoracoabdominal aortic aneurysms

The unfavorable vessel anatomy is still a major challenge in the endovascular aneurysm repair,with usually insufficient or even no proximal/distal landing zone for the stent-graft.During recent years,several articles have been published concerning the new approach of multiple stents to the treatment of aneurysm by reducing the stent porosity to encourage laminar flow,preserving branch patency,and promoting thrombus formation in the aneurysm.1,2 We herein report the use of multiple overlapping stents in the treatment of thoracoabdominal aortic aneurysms.